The long-term objective of this project is to investigate the molecular mechanism of neuropathic pain resulting from peripheral nerve injuries. These disorders do not typically respond to conventional analgesics, and represent major problems affecting the quality of daily life of patients. Unfortunately, the molecular mechanisms of neuropathic pain are poorly understood and, as a consequence, there are no specifically targeted, effective pharmacological agents available for neuropathic pain treatment. Our preliminary data indicate a correlation between increased expression, in sensory neurons and spinal cord, of alpha 2 delta calcium channel subunit and neuropathic pain development in a rat model of peripheral nerve injury. This suggests that altered alpha 2 delta calcium channel subunit expression or its modulation to functional calcium channels may underline the neuronal plasticity following peripheral nerve injury, and play a role in neuropathic pain processing. Using molecular, immunohistochemical and pharmacological techniques, this research proposal is designed to test this hypothesis by examining 1) the possible roles of spinal alpha 2 delta subunit expression in neuropathic pain development and 2) the cellular mechanisms of nerve injury-induced alteration in alpha 2 delta subunit expression in spinal cord and sensory neurons.